5-HTP for Migraine Prevention

How 5-HTP May Help Your Headaches and What to Watch Out For

A supplement called 5-hydroxytryptophan (5-HTP), or oxitriptan, has been considered among one of the alternative treatments for headaches and migraines. The body converts this substance to 5-hydroxytryptamine (5-HT), also known as serotonin, a neurotransmitter that mediates mood and pain.

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Serotonin, Migraines, and Headaches

Low serotonin levels are typically found in those with depression, but migraineurs and people with chronic headache disorders can have low serotonin levels too— both during and in between attacks. It isn't quite clear why migraines and serotonin are related. The most popular theory is that a deficit in serotonin makes a person hypersensitive to pain.

Because of this association, several methods of augmenting serotonin activity in the brain are commonly used to prevent migraines and to treat acute episodes.

  • Selective serotonin reuptake inhibitors (SSRIs): SSRIs are a category of prescription antidepressants that prolong the action of serotonin in the brain. They are often taken on a daily basis to prevent migraine attacks.
  • Triptans: A group of powerful prescription medications, triptans work by binding to serotonin receptors, imitating their action. They are used to stop severe migraine attacks.
  • Complementary and alternative therapy (CAM): Some of the natural methods that have been found effective for migraine prevention include acupuncture, meditation, and exercise. These are all believed to produce their anti-migraine effect by increasing serotonin levels.

What Is 5-HTP?

5-HTP is an amino acid produced by the human body from the essential amino acid L-tryptophan, which must be obtained through your diet. L-tryptophan can be found in foods like seeds, soybeans, turkey, and cheese. Enzymes naturally convert L-tryptophan into 5-HTP and then convert 5-HTP into 5-HT. 

5-HTP supplements are made from the plant Griffonia simplicifolia, a West African medicinal plantThis supplement has been used for depression, fibromyalgia, chronic fatigue syndrome, and as an aid for weight loss, but there is no strong evidence to show that it is beneficial.

When considering 5-HTP or any natural supplement, it's important to understand that these products are chemicals. If you are taking them because they could be powerful enough to achieve a positive effect on your health, keep in mind that they can be strong enough to produce negative effects as well.

Research on 5-HTP for Migraines

It is not clear whether 5-HTP supplements are beneficial for migraines or other types of headaches. Overall, there is limited research; some studies suggest that it helps, and others fail to show any effect.

  • A 2017 research experiment using rats showed that 5-HTP supplementation helped prevent estrogen-associated changes in the brain that are consistent with migraine with aura. This suggests that 5-HTP may exert its action by reducing the effects of migraine triggers.
  • 5-HTP was used in two siblings with a rare type of migraine that is associated with stroke-like symptoms called hemiplegic migraine. A 2011 report described an improvement of their symptoms in response to 5-HTP.
  • A 2003 report that used a large database to evaluate migraine prevention in children found that 5-HTP did not have any impact in reducing the frequency of episodes.


Migraine studies use a dose of 5-HTP ranging between 25 mg per day to 200 mg per day for adults. There are no well-established or recommended doses for this supplement at this time, but it's important to note that higher doses are associated with side effects and drug interactions.

This supplement is not recommended for children.

Side Effects and Safety

5-HTP has been associated with several side effects, including:

  • Nausea
  • Bloating
  • Flatulence
  • Loose stools or diarrhea

Drug Interactions

5-HTP may interact with certain medications, including carbidopa, which is used to treat Parkinson's disease. It can also interact with triptans, SSRIs, and monamine oxidase inhibitors (MAOIs, another category of antidepressants).

Contaminant Concern

Tryptophan and 5-HTP supplements can be contaminated with a naturally occurring component, 4,5-tryptophan-dione, a neurotoxin also described as Peak X. Muscle aches, cramps, and fevers can result from the inflammatory effects of Peak X. Long term effects can include muscle and nerve damage.

Because this chemical is a byproduct of a chemical reaction rather than an impurity or a pollutant, it can be found in supplements even when their preparation is done under sanitary conditions.

It is vital that you discuss taking any supplements with your healthcare provider or pharmacist to ensure they are safe for you and do not interact with your other medications.

Remember, dietary and herbal supplements have not undergone the same scrutiny and testing as over-the-counter and prescription medications, which means that studies proving their effectiveness and their safety are limited or have not been done.       

A Word From Verywell

Supplements and natural treatments can be appealing, particularly if they do not have side effects. Indeed, natural treatments have been found effective for a number of conditions. There is evidence that magnesium supplements may reduce the frequency and severity of migraine attacks. At the current time, however, it isn't clear whether 5-HTP is beneficial for migraines or not.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Horvath GA, Selby K, Poskitt K, et al. Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotoninCephalalgia. 2011;31(15):1580-1586. doi:10.1177/0333102411420584.

  2. Aggarwal M, Puri V, Puri S. Serotonin and CGRP in migraineAnn Neurosci. 2012;19(2):88–94. doi:10.5214/ans.0972.7531.12190210

  3. Chauvel V, Multon S, Schoenen J. Estrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura. Cephalalgia. 2018;38(3):427-436. doi:10.1177/0333102417690891

  4. Victor S, Ryan SW. Drugs for preventing migraine headaches in children. Cochrane Database Syst Rev. 2003;(4):CD002761. doi:10.1002/14651858.CD002761

  5. Icahn School of Medicine at Mount Sinai. 5-Hydroxytryptophan (5-HTP).

  6. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150(1):111-22. doi:10.1016/j.toxlet.2003.12.070

By Teri Robert
 Teri Robert is a writer, patient educator, and patient advocate focused on migraine and headaches.